MAP30 is a ribosome inactivating protein (RIP) derived from bitter melon. RIPs are of wide interest because they are cell toxins with potent anti-viral/anti-tumor activities. We have recently shown that the solution structure of MAP30 is similar to the crystal structures of other RIPs; hence, there is no obvious structural basis for reported activities unique to MAP30, such as inhibition of HIV integrase. Our hypothesis that this reported activity might reflect competition of MAP30 and integrase for a common DNA substrate was supported by (1) chemical shift perturbation data upon adding a target DNA and (2) the fact that NaBH4 traps an imine cross-link between MAP30 and LTR RNA. These observations provide evidence that, after binding, MAP30 depurinates DNA and acts as DNA lyase. Further Biochemical studies showed that MAP30 specifically depurnated adenine sites in DNA targets. Based upon the biochemical data and detailed structural analysis we proposed that RIPs utilize a common active site to depurinate both DNA and 28SrRNA, and that, following depurination of DNA, the apurinic DNA site interacts with the neighboring conserved Trp sidechain, thus facilitating nucleophilic attack by a nearby Lys sidechain.